<p>Parthenolide Inhibits Angiogenesis in Esophageal Squamous Cell Carcinoma Through Suppression of VEGF</p>

Abstract

Background: Parthenolide (PT), the effective active ingredient of the medicinal plant, feverfew (Tanacetum parthenium), has been used as an anti-inflammatory drug due to its involvement in the inhibition of the NF-кB pathway. Moreover, recent studies have demonstrated the anti-tumor effect of PT in several cancers. However, the effect of PT on esophageal carcinoma remains unclear to date. In this study, we examined the inhibitory effects of PT and its underlying mechanism of action in human esophageal squamous cell carcinoma (ESCC) cells-Eca109 and KYSE-510. Methods: The proliferation ability of Eca109 and KYSE-510 treated with PT was detected using the Cell Counting Kit-8 and colony forming assay. The Transwell assay and the wound healing assay were used to analyze the cell invasion and migration ability, respectively. The tube formation assay was used to investigate the effect of PT on tube formation of endothelial cells. The expression level of NF-кB, AP-1 and VEGF was analyzed by Western blot. Results: We demonstrated that PT attenuates the proliferation and migration ability of ESCC cells in vitro and also inhibits tumor growth in the mouse xenograft model. In addition, PT exhibited anti-angiogenesis activity by weakening the proliferation, invasion and tube formation of endothelial cells in vitro and reduced microvessel density in the xenograft tumors. Further studies revealed that PT reduced the expression level of NF-кB, AP-1 and VEGF in ESCC cells. Conclusion: Collectively, the results of our study demonstrated that PT exerts anti-tumor and anti-angiogenesis effects possibly by inhibiting the NF-кB/AP-1/VEGF signaling pathway on esophageal carcinoma and might serve as a promising therapeutic agent for ESCC.

Dandelion Seed Extract Affects Tumor Progression and Enhances the Sensitivity of Cisplatin in Esophageal Squamous Cell Carcinoma

“…Matrix metalloproteinases (MMP2 and MMP9) not only release growth factors to promote the growth of tumor cells, but also promote cell shedding to facilitate the invasion and metastasis of tumor cells ( Li et al, 2019 ; Tian et al, 2020 ). In addition, it can also activate VEGF to accelerate angiogenesis by initiating protein degradation of the vascular basement membrane, opening the pathway for endothelial cell metastasis to form new blood vessels ( Tang et al, 2019 ).…”

“…PI3K is a potential therapeutic target with the highest mutation frequency of ESCC and plays a vital role in ESCC cell proliferation ( Wang et al, 2020 ). Matrix metalloproteinases facilitate the invasion and metastasis of tumor cells and can activate VEGF to accelerate angiogenesis ( Li et al, 2019 ; Tian et al, 2020 ). Meanwhile, The important biological process for epithelial-derived malignant tumor cells to acquire the ability to migrate and invade is EMT ( Forghanifard et al, 2020 ; Ren et al, 2020 ).…”

“…PI3K is a potential therapeutic target with the highest mutation frequency of ESCC ( Wang et al, 2020 ; Yu et al, 2020 ). Survivin, Bax, Bcl-2 and caspase3/9 are apoptosis-related genes associated with esophageal cancer ( Pan et al, 2015 ; Liu et al, 2018 ; Zhou et al, 2018 ), and MMP2/9, VEGF and EMT processes are involved in the metastasis of esophageal cancer ( Li et al, 2019 ; Forghanifard et al, 2020 ; Ren et al, 2020 ; Tian et al, 2020 ). Therefore, in the present study, we detected the effects of dandelion seed extract (DSE) on the factors involving the carcinogenesis of esophageal cancer to explore the mechanism of dandelion seed extract against ESCC.…”

The Emerging Potential of Parthenolide Nanoformulations in Tumor Therapy

“… 64 In addition, NF-κB inactivation by PTL sensitized gastric tumor and esophageal squamous cell carcinoma (ESCC) cells to chemotherapeutic drugs including ADM and cisplatin. 78 , 79 PTL exerted its anti-angiogenic effects by inhibiting the NF-кB-mediated VEGF expression in ESCC cells. 79 Moreover, several studies have pointed out that PTL inhibits migration, invasion, and metastasis, which benefits from its abilities to regulate epithelial-to-mesenchymal transition (EMT) and to inhibit FAK1, TCP, and STAT3.…”

“…78 , 79 PTL exerted its anti-angiogenic effects by inhibiting the NF-кB-mediated VEGF expression in ESCC cells. 79 Moreover, several studies have pointed out that PTL inhibits migration, invasion, and metastasis, which benefits from its abilities to regulate epithelial-to-mesenchymal transition (EMT) and to inhibit FAK1, TCP, and STAT3. 33 , 80–83 …”